83 Shipping-associated particulate matter enhances viral susceptibility and heightens inflammatory responses in bronchial and alveolar epithelial cells

Abstract Background Exposure to airborne particulate matter (PM) has been associated with adverse effects on the respiratory system. Shipping-associated PM is an important contributor to airborne PM in port and coastal areas, but composition-specific effects are poorly understood. Objective To investigate the effects of shipping-associated PM on bronchial and alveolar epithelial cells. Methods Coarse, fine and ultrafine PM (UFPM) was collected near a cruise shipping terminal at the Port of Southampton. Composition was characterised by inductively coupled plasma-mass spectrometry. 16HBE14o- bronchial epithelial cells exposed to 100 µg/mL PM for 24 h were analysed transcriptomically by RNA-seq. Effects of metals enriched in cruise ship UFPM were studied in alveolar epithelial cells (AEC). Gene and protein expression were measured by RT-qPCR, and Western blotting, and inflammatory mediator release by ELISA. Effects on viral replication were studied by viral copy number RT-qPCR in human primary bronchial epithelial cells infected with rhinovirus-16 (RV-16), and focus-forming assay in VeroE6 cells infected with SARS-CoV-2. Results Cruise shipping-associated UFPM was enriched in vanadium, nickel and cobalt, inducing inflammatory mediator release in 16HBE14o-. RNA-Seq revealed significant UFPM-induced downregulation of interferon signalling pathways. In AEC this was recapitulated by vanadium, inducing downregulation of antiviral genes (ISG15: 0.22-fold, IFIT1: 0.10-fold, P ≤ 0.05). Similar vanadium-mediated inhibition was observed following stimulation by interferon-β- and poly(I:C). Replication of RV16 and SARS-CoV-2 was increased by vanadium exposure. Conclusions Shipping-associated UFPM impairs antiviral signalling and drives a pro-inflammatory response, effects recapitulated by vanadium. Further research is needed to understand the implications of these findings in vivo.